title: Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: recommendations for patient information.
abstract: BACKGROUND
  Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug.
  
  
  METHODS
  We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the "proportion of symptoms non-pharmacological".
  
  
  RESULTS
  28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73-89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70-95), and hyperglycaemia 83/100 (68-98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21-44) and intermittent claudication (41/100, 2-81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p<0.01) and insomnia (by 27%, p=0.01).
  
  
  CONCLUSIONS
  Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths.
authors.affiliation: National Heart and Lung Institute, Imperial College London, UK; St Mary's Hospital, Imperial College Healthcare NHS Trust, UK. Electronic address: anthonybarron@hotmail.co.uk.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Barron
authors.forename: Nabeela
authors.initials: N
authors.lastname: Zaman
authors.forename: Graham D
authors.initials: GD
authors.lastname: Cole
authors.forename: Roland
authors.initials: R
authors.lastname: Wensel
authors.forename: Darlington O
authors.initials: DO
authors.lastname: Okonko
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced / Q000175:diagnosis; D004244:Dizziness / Q000139:chemically induced / Q000175:diagnosis; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000175:diagnosis; D015990:Placebo Effect; D017410:Practice Guidelines as Topic / Q000592:standards*; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: Beta-blockers; Heart failure; Side-effects